This competitive renewal application requests continuing support for a training program that provides predoctoral graduate students with broad state-of-the-art training in Systems and Integrative Biology. Students will learn and apply tools and approaches of genomics, bioinformatics, proteomics as well as cell and molecular biology to the study of integrated systems and organismic biology. The program is centered in the Department of Molecular & Integrative Physiology because of the Department's longstanding commitment to integrative biology, but students will enter after their initial year in a combined gateway Program in Biomedical Sciences (PIBS) and can be enrolled in multiple PhD programs including Physiology, Pharmacology, Neuroscience, Cell and Molecular Biology, Molecular and Cellular Pathology, Cell and Developmental Biology, Human Genetics, Biochemistry, Bioinformatics and the Medical Scientist Training Program. Trainees will usually be supported for their second and third years. Therefore, the six available slots are usually assigned to three new trainees and three reappointed trainees each year. The potential applicant pool is all students applying to PIBS and includes both students who come to Michigan to study integrative biology and those who enter undecided and are then drawn to integrative biology. The training includes formal coursework and seminars, teaching, and research experiences with faculty in a variety of departments at the University of Michigan. All students will take graduate level courses in Integrative Biology, Cell & Molecular function, Genetics & Molecular Biology, and Computational Biology. Additional courses are selected by the student in accordance with his/her interests. Students also participate in a course on Responsible Conduct of Research and weekly student research seminars in their respective PhD programs in which they are expected to critically evaluate the presentations of their peers. Rather than offering a standard journal club, our program has a highly interactive monthly workshop where the trainees work together with faculty to apply the principles of mathematical modeling and computational biology to a real set of data from one of the participating faculty's research programs. This broad training is further reinforced by each student taking a written and oral preliminary or candidacy examination mid-way or at the end of the second year of study that requires an understanding of biological function, from the cellular and molecular level to that of the whole animal including interactions between the environment and the organism. A unique aspect of this training program is that all students have two dissertation co-chairs, rather than the more traditional single chair, at least one of whom will be schooled in the most recent techniques in cellular, molecular, or computational biology and one being an integrative biologist. The training faculty consists of 52 outstanding scientists all of whom are experts either in cellular and molecular or systems and integrative biology and committed to training individuals to answer questions of integrative physiological relevance.